SARS1
seryl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II
Basic information
Region (hg38): 1:109213917-109238182
Previous symbols: [ "SARS" ]
Links
Phenotypes
GenCC
Source:
- autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Neurodevelopmental disorder with microcephaly, ataxia, and seizures | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal; Neurologic | 28236339 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (8 variants)
- Neurodevelopmental disorder with microcephaly, ataxia, and seizures (5 variants)
- Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome (2 variants)
- Cerebral arteriovenous malformation (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SARS1 gene is commonly pathogenic or not.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 1 | 3 | 1 | 5 | ||
missense | 2 | 1 | 1 | 1 | 5 | |
nonsense | 0 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 0 | |||||
splice variant | 1 | 2 | 3 | |||
non coding | 2 | 2 | ||||
Total | 2 | 1 | 2 | 5 | 5 |
Variants in SARS1
This is a list of pathogenic ClinVar variants found in the SARS1 region.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
1-109214118-G-A | See cases | Uncertain significance (Oct 06, 2021) | ||
1-109228386-C-T | Inborn genetic diseases | Uncertain significance (Jun 01, 2023) | ||
1-109228441-T-C | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Benign (Nov 07, 2021) | ||
1-109229572-G-A | Benign (Dec 31, 2019) | |||
1-109230944-G-A | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Pathogenic (Jul 01, 2022) | ||
1-109231677-G-T | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Likely pathogenic (-) | ||
1-109235353-G-T | Likely benign (Dec 31, 2019) | |||
1-109235366-C-T | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Pathogenic (Apr 19, 2023) | ||
1-109235412-G-A | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Uncertain significance (Apr 27, 2019) | ||
1-109235430-AGGT-A | Uncertain significance (Jun 21, 2023) | |||
1-109235955-T-C | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Benign (Nov 07, 2021) | ||
1-109235978-T-C | Cerebral arteriovenous malformation | Pathogenic (Feb 14, 2018) | ||
1-109236048-C-T | Likely benign (Jan 30, 2018) | |||
1-109236451-G-A | Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome | Benign/Likely benign (Sep 27, 2021) | ||
1-109236459-C-T | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Pathogenic (Apr 19, 2023) | ||
1-109236487-C-T | Neurodevelopmental disorder with microcephaly, ataxia, and seizures | Pathogenic (Jun 22, 2023) | ||
1-109236555-G-A | Benign (Mar 29, 2018) | |||
1-109237312-G-A | Benign (Dec 31, 2019) | |||
1-109237381-T-C | Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome | Benign/Likely benign (Feb 15, 2022) | ||
1-109237799-A-C | Inborn genetic diseases | Uncertain significance (Aug 19, 2023) | ||
1-109237810-G-A | Likely benign (Dec 31, 2019) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SARS1 | protein_coding | protein_coding | ENST00000234677 | 11 | 24252 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.999 | 0.000749 | 125744 | 0 | 3 | 125747 | 0.0000119 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 2.66 | 170 | 299 | 0.568 | 0.0000170 | 3378 |
Missense in Polyphen | 36 | 114.75 | 0.31372 | 1309 | ||
Synonymous | 1.48 | 94 | 114 | 0.823 | 0.00000639 | 973 |
Loss of Function | 4.70 | 2 | 29.6 | 0.0675 | 0.00000175 | 321 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00 | 0.00 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.0000176 | 0.0000176 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.00 | 0.00 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser- AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229, PubMed:28236339). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000). {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848, ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:9431993}.;
- Disease
- DISEASE: Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) [MIM:617709]: An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness. {ECO:0000269|PubMed:28236339}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Aminoacyl-tRNA biosynthesis - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);tRNA Aminoacylation;Translation;Selenocysteine synthesis;Metabolism of proteins;Metabolism of amino acids and derivatives;Glycine Serine metabolism;selenocysteine biosynthesis;Metabolism;tRNA charging;Selenoamino acid metabolism;Cytosolic tRNA aminoacylation
(Consensus)
Recessive Scores
- pRec
- 0.261
Intolerance Scores
- loftool
- 0.145
- rvis_EVS
- -0.32
- rvis_percentile_EVS
- 31.69
Haploinsufficiency Scores
- pHI
- 0.190
- hipred
- Y
- hipred_score
- 0.749
- ghis
- 0.547
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sars
- Phenotype
Zebrafish Information Network
- Gene name
- sars
- Affected structure
- trunk vasculature
- Phenotype tag
- abnormal
- Phenotype quality
- branchiness
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;translation;tRNA aminoacylation for protein translation;seryl-tRNA aminoacylation;tRNA processing;selenocysteine metabolic process;negative regulation of angiogenesis;selenocysteinyl-tRNA(Sec) biosynthetic process;negative regulation of vascular endothelial growth factor production
- Cellular component
- nucleus;cytoplasm;cytosol;extracellular exosome
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA binding;serine-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;selenocysteine-tRNA ligase activity